FNH 351 - Vitamins and Energy Metabolism #3

Thiamin

what is the free form of thiamin? what is the active form?

→ free form:

• thiamin

→ active form:

• thiamin diphosphate (TDP)

what form of thiamin is found in foods of plant origin?

free form (non-phosphorylated)

what form of thiamin is found in foods of animal origin?

• thiamin diphosphate (TDP, 95%)

• thiamin mono- and tri-phosphate (TMP + TTP, 5%)

what form of thiamin is found in supplements/fortified foods?

free form

examples of food sources containing thiamin?

salmon, nuts, legumes, grain products

what factors impact dietary thiamin?

1. sensitive to sulfite

2. heat destruction of thiamin - pH dependent (pH ≥ 8 potential heat destruction of thiamin, pH < 8 heat stable)

3. antithiamin factors

what antithiamin factors impact dietary thiamin?

1. thiaminases

2. polyhydroxyphenols

what do thiaminases do?

catalyze destruction of thiamin in raw fish and shellfish. They are thermolabile enzymes so cooking deactivates them

what do polyhydroxyphenols do?

inactivate thiamin/destruction of thiazole ring. Thermostable. Presence of vitamin C can prevent destruction

how is thiamin digested?

if free thiamin, can be readily absorbed without digestion. If phosphorylated forms, require dephosphorylation; catalyzed by phosphatases in small intestine

where does thiamin absorption take place in?

duodenum and jejunum

how is thiamin absorbed?

1. active transport through thiamine transporters ThTr1 and ThTr2. Sensitive to pH changes, and saturation of the transporters occurs at >5mg

2. passive diffusion at intake levels > 2.5 mg

what can alcohol do to thiamin absorption?

can inhibit expression of ThTr1 and ThTr2

where does thiamin go after crossing the basolateral membrane?

thiamin is released into the blood within 1-2 hours and is distributed to tissues via the blood system

how is thiamin transported?

its distributed to tissues via bloodsteam. 90% of circulating thiamin is present in RBCs and WBCs. Thiamin enters RBC by facilitated diffusion (the higher the circulating thiamin levels, the higher the uptake of thiamin into RBCs). Some thiamin, free or bound to albumin, and TMP are found in plasma.

describe the uptake of thiamin into cells

uptake of thiamin done thru active transport (ThTr1 and ThTr2). Mostly taken up by liver (ThTr2) and skeletal muscle (ThTr1), and some by other organs. Phosphorylation of thiamin upon cellular uptake

total body thiamin: ___ mg

25-30 mg

where is thiamin stored?

Skeletal muscles contain about half of total body thiamin. Other storage includes liver, heart, and kidneys

whats the half-life of thiamin?

9-20 days

how is thiamin excreted?

through the kidney → urinary excretion. oocurs if body thiamin > above tissue needs and storage capacity. It is excreted either intact or catabolized.

what is the metabolic function of thiamin?

TPD acts as a coenzyme in major decarboxylation reactions and energy metabolism:

1. entry of TCA cycle (pyruvate → acetyl-CoA)

2. half-way around TCA cycle (alpha-ketoglutarate → succinyl-CoA)

3. transketolase reactions in hexose monophosphate shunt which is an alternative pathway for oxidation of glucose, major source of ribose for DNA and RNA, and necessary for the production of NADPH in tissues actively engaged in biosynthesis

in thiamin deficiency, what happens to oxidation of glucose?

it is impaired with no alternative route

what non-coenzyme function does thiamin have?

• Nervous system function

  • Exact role unclear.

  • Proposed role:

    • Influences nerve impulse transmission through

      • Maintenance of nerve membrane function

      • Synthesis of myelin & neurotransmitters

what disease can thiamin deficiency cause?

beriberi

symptoms of beriberi

weight loss, weakness, impaired sensory perception, irregular heart rate, possibly edema

what can sevre cases of beriberi cause?

Damage to neurological system & cardiovascular system

what are the different classifications of beriberi?

• dry beriberi

• wet beriberi

• infantile beriberi

• gastrointestinal beriberi

what are characteristics of dry beriberi?

• affects the peripheral nervous system

• Occurs in adults

• Cause: chronic low thiamin intake especially if coupled with high carbohydrate intake

• Severe muscle weakness and wasting

• Peripheral neuropathy

  • sensory and motor nerve conduction problems

  • mostly distal parts of the limbs (feet and hands)

what is wernickle encephalopathy?

a form of dry beriberi, commonly caused by chronic alcoholism

what are symptoms of wernickle encephalopathy

• Symptoms

  • Abnormal eye movement

  • Ataxic gait (normal, uncoordinated movements)

  • Cognitive impairment

• severe causes include Korsakoff psychosis = amnesia (memory loss), little/no working memory, confusion

what are characteristics of wet beriberi?

• affects cardiovascular and other systems

• More extensive cardiovascular system damage

  • Cardiomegaly (enlarged heart)

  • Tachycardia (rapid heartbeat)

  • Heart failure (also affecting the lungs)

• Peripheral edema

characteristics of acute beriberi

• infantile beriberi

• Occurs mostly in infants (e.g., breastfed by mothers with low thiamin)

• Gastrointestinal symptoms: anorexia, nausea, vomiting

• Cardiovascular symptoms: rapid heartbeat, cardiomegaly

• Lactic acidosis

what are the risk factors and causes for deficiency of thiamin?

→ Rare in healthy individuals with access to a variety of thiamin rich foods

→ In higher income countries, thiamin deficiency more common with:

1. Alcoholism

   • Decreased food consumption (low thiamin intake)

   • Reduced thiamin absorption (impaired by alcohol)

   • Diminished thiamin utilization (liver damage)

2. Health conditions that lead to increased thiamin needs, e.g.,

   • cancer or HIV/AIDS

   • inflammatory bowel diseases

   • diuretics or dialysis

   • bariatric surgery

where is thiamin deficiency more common? what are the common causes of thiamin deficiency here?

• more common in low-middle income countries

• lack of diverse food, reliance on low-thiamin staples like white rice, and consumption of thiamin inhibitors in some cultures

what RDA is established for thiamin? do males or females have a higher RDA?

• EAR

• males

is there a UL for thiamine?

no